Diphenhydramine - perhaps known most commonly as its brand name formulation Benadryl - is a first-generation H1 receptor antihistamine that is used extensively for the treatment of seasonal allergies, insect bites and stings, and rashes ^9,10,11,15. However, it also has antiemetic, antitussive, hypnotic, and antiparkinson properties ^11,14. As histamine receptors exist both peripherally and in the central nervous system, diphenhydramine has been shown to cause sedation due to its competitive antagonism of histamine H1 receptors within the central nervous system ^9,10,11,15,5. While its use in allergy therapy can sometimes fall out of favor due to its sedative effect, diphenhydramine has been repurposed for use within many non-prescription over-the-counter sleep aids and cough-and-cold medications that have been marketed for "night time" use ^9,12,13.

Diphenhydramine is also used in combination with 8-chlorotheophylline as the anti-nausea drug Dimenhydrinate where it is utilized primarily for its antagonism of H1 histamine receptors within the vestibular system ⁴.

Diphenhydramine has also been shown to be implicated in a number of neurotransmitter systems that affect behaviour including dopamine, norepinephrine, serotonin, acetylcholine, and opioid ³. As a result, diphenhydramine is being investigated for its anxiolytic and anti-depressant properties.

Structure

Similar Structures

Synonyms

2-(benzhydryloxy)-N,N-dimethylethylamine
2-diphenylmethoxy-N,N-demthylethanamine
Difenhidramina
Diphenhydramine
Diphenhydraminum
N-(2-(diphenylmethoxy)ethyl)-N,N-dimethylamine
O-benzhydryldimethylaminoethanol
α-(2-dimethylaminoethoxy)diphenylmethane
β-dimethylaminoethanol diphenylmethyl ether
β-dimethylaminoethyl benzhydryl ether

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Diphenhydramine citrate	4OD433S209	88637-37-0	SPCKHVPPRJWQRZ-UHFFFAOYSA-N
Diphenhydramine hydrochloride	TC2D6JAD40	147-24-0	PCHPORCSPXIHLZ-UHFFFAOYSA-N
Diphenhydramine methylbromide	UJO67AO8YI	31065-89-1	BDQPXVWYFLTETB-UHFFFAOYSA-M
Diphenhydramine salicylate	707L3YC54L	7491-10-3	RTSZUSOHOIFYSY-UHFFFAOYSA-N

Active Moieties

Name	Kind	UNII	CAS	InChI Key
Phenol	unknown	339NCG44TV	108-95-2	ISWSIDIOOBJBQZ-UHFFFAOYSA-N

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Benadryl	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	Parke Davis Div Of Pfizer Inc	1957-12-30	2007-01-31
Benadryl	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	Parke Davis Div Of Pfizer Inc	1947-03-06	2008-01-31
Benadryl	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	Physicians Total Care, Inc.	1994-06-01	2010-12-29
Benadryl	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	Physicians Total Care, Inc.	2006-01-13	2010-12-29
Benadryl Inj. 50mg/ml	Liquid		Intramuscular; Intravenous	Warner Lambert Canada Inc.	1994-12-31	2000-11-27
Dicopanol	Kit	0.86 g/0.86g	Oral	California Pharmaceuticals, Llc	2016-01-01	Not applicable
Dicopanol	Kit	0.75 g/0.75g	Oral	Fusion Pharmaceuticals LLC	2010-02-08	Not applicable
Diphenhydramine HCl Inj USP 50mg/ml	Liquid		Intravenous	International Medication Systems, Limited	1974-12-31	1997-08-15
Diphenhydramine HCl Injection, USP	Solution		Intramuscular; Intravenous	Sterimax Inc	1994-12-31	Not applicable
Diphenhydramine Hydrochloride Injection	Solution		Intramuscular; Intravenous	Fresenius Kabi	2012-02-17	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

Learn more

Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

Learn more

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Diphen	Solution	12.5 mg/5mL	Oral	Foxland Pharmaceuticals, Inc.	2019-09-11	Not applicable
Diphendydramine Hydrochloride	Capsule	25 mg/1	Oral	Remedy Repack	2010-12-17	2017-04-24
Diphenhydramine	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	Micro Labs Limited	2018-12-04	Not applicable
Diphenhydramine	Injection, solution	50 mg/1mL	Intravenous	Remedy Repack	2013-11-18	2017-01-20
Diphenhydramine	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	Fresenius Kabi USA, LLC	2002-08-01	Not applicable
Diphenhydramine	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	Micro Labs Limited	2019-12-10	Not applicable
Diphenhydramine Hci	Injection, solution	50 mg/1mL	Intramuscular; Intravenous	HF Acquisition Co LLC, DBA HealthFirst	2018-11-19	Not applicable
Diphenhydramine Hydrochloride	Injection	50 mg/1mL	Intramuscular	Remedy Repack	2011-12-16	2015-05-20
Diphenhydramine Hydrochloride	Solution	12.5 mg/5mL	Oral	Pharmaceutical Associates, Inc.	1982-02-10	Not applicable
Diphenhydramine Hydrochloride	Capsule	50 mg/1	Oral	Barr Laboratories	1972-09-01	2014-07-31

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

Learn more

Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

Learn more

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
7 Select Allergy	Tablet	25 mg/1	Oral	7-Eleven	2014-04-22	2021-02-28
7 Select Allergy Childrens	Solution	12.5 mg/5mL	Oral	7-Eleven	2014-08-05	2021-04-30
7 Select Night Time Sleep Aid	Solution	50 mg/30mL	Oral	7-Eleven	2014-04-22	2021-05-31
Adult Allergy	Solution	50 mg/20mL	Oral	Chain Drug Consortium, LLC	2015-05-04	Not applicable
Adult Allergy Relief	Solution	50 mg/20mL	Oral	Wal-Mart Stores, Inc.	2017-05-03	Not applicable
After Bite Outdoor	Gel	20 mg/1mL	Topical	Tender Corporation	2016-11-01	2018-03-01
After Bite Outdoor	Gel	20 mg/1g	Topical	Tender Corporation	2018-03-01	Not applicable
After Bite Plus	Gel	20 mg/1g	Topical	Tender Corporation	2018-03-01	Not applicable
After Bite Plus	Cream	20 mg/1mL	Topical	Tender Corporation	2012-07-03	2018-03-06
After Bite Xtra	Gel	20 mg/1mL	Topical	Tender Corporation	2016-11-01	2018-03-06

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

Learn more

Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

Learn more

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
7 Select Ibuprofen PM	Diphenhydramine citrate (38 mg/1) + Ibuprofen (200 mg/1)	Tablet, film coated	Oral	7-Eleven	2014-08-05	2020-11-30
7 Select Night Time Severe Cold Cough and Flu	Diphenhydramine hydrochloride (25 mg/1) + Acetaminophen (650 mg/1) + Phenylephrine hydrochloride (10 mg/1)	Powder, for solution	Oral	7-Eleven	2016-01-25	2021-01-01
7 Select Night Time severe cold, cough and flu	Diphenhydramine hydrochloride (25 mg/1) + Acetaminophen (650 mg/1) + Phenylephrine hydrochloride (10 mg/1)	Powder, for solution	Oral	7 Eleven	2015-11-12	2017-08-01
7 Select Pain Relief PM	Diphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)	Tablet, film coated	Oral	7 Eleven	2014-09-04	2016-07-22
7-Select Advil PM	Diphenhydramine citrate (38 mg/1) + Ibuprofen (200 mg/1)	Tablet, coated	Oral	Lil' Drug Store Products, Inc.	2011-06-01	2017-12-31
Acedif PLUS	Diphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)	Tablet	Oral	Plus Distributors LLC	2019-02-01	Not applicable
Aceta-gesic	Diphenhydramine hydrochloride (12.5 mg/1) + Acetaminophen (325 mg/1)	Tablet, coated	Oral	Rugby	2014-06-30	Not applicable
Aceta-gesic	Diphenhydramine hydrochloride (12.5 mg/1) + Acetaminophen (325 mg/1)	Tablet, coated	Oral	Remedy Repack	2014-08-08	Not applicable
Acetadryl	Diphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)	Tablet, film coated	Oral	Physicians Science & Nature Inc.	2011-07-21	2016-05-31
Acetadryl	Diphenhydramine hydrochloride (25 mg/1) + Acetaminophen (500 mg/1)	Tablet, film coated	Oral	Aidarex Pharmaceuticals LLC	2011-07-21	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Airacof	Diphenhydramine hydrochloride (12.5 mg/5mL) + Codeine phosphate hemihydrate (7.5 mg/5mL) + Phenylephrine hydrochloride (7.5 mg/5mL)	Liquid	Oral	Centurion Labs	2010-01-08	2016-05-02
Antiphlamine Coin Plaster	Diphenhydramine (0.246 mg/0.2832g) + Levomenthol (2.769 mg/0.2832g) + Synthetic camphor (1.108 mg/0.2832g)	Patch	Topical	Hanul Trading Co., Ltd.	2016-10-10	2017-04-14
Antiphlamine Coin Plaster	Diphenhydramine (0.246 mg/0.2832g) + DL-alpha-Tocopherol (0.308 mg/0.2832g) + Levomenthol (2.769 mg/0.2832g) + Methyl salicylate (5.541 mg/0.2832g) + Nonivamide (0.046 mg/0.2832g) + Peppermint oil (0.693 mg/0.2832g) + Synthetic camphor (1.108 mg/0.2832g)	Patch	Topical	Hanul Trading Co., Ltd.	2016-10-10	Not applicable
Benadryl	Diphenhydramine hydrochloride (50 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Physicians Total Care, Inc.	1994-06-01	2010-12-29
Benadryl	Diphenhydramine hydrochloride (50 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Physicians Total Care, Inc.	2006-01-13	2010-12-29
Contrast Allergy PreMed Pack	Diphenhydramine hydrochloride (50 mg/50mg) + Prednisone (50 mg/50mg)	Kit	Oral	Shertech Laboratories, Llc	2016-09-13	Not applicable
Dermagesic	Diphenhydramine hydrochloride (1 mg/100mL) + Phenol (1.4 mg/100mL)	Liquid	Topical	Llorens Pharmaceuticals International Division	2009-02-01	2014-01-20
Dicopanol	Diphenhydramine hydrochloride (0.86 g/0.86g)	Kit	Oral	California Pharmaceuticals, Llc	2016-01-01	Not applicable
Dicopanol	Diphenhydramine hydrochloride (0.75 g/0.75g)	Kit	Oral	Fusion Pharmaceuticals LLC	2010-02-08	Not applicable
Diphenhydramine HCl	Diphenhydramine hydrochloride (25 mg/1)	Capsule	Oral	Cardinal Health	2011-06-03	2015-05-31

International/Other Brands

Aleryl / Alledryl / Allerdryl (Valeant) / Belix / Benylan (Biogen) / Dermodrin (Montavit) / Desentol (Meda) / Dibondrin (Montavit) / Dimedrol (Zdorovie) / Diphen (Wockhardt) / Dormarex 2 / Genahist / Histaxin (Meda) / Hyrexin (Hyrex) / Nytol Quickgels (GlaxoSmithKline) / Restamin (Kowa Souyaku) / Siladryl / Silphen Cough

Categories

UNII

8GTS82S83M

CAS number

58-73-1

Weight

Average: 255.3547
Monoisotopic: 255.162314299

Chemical Formula

C₁₇H₂₁NO

InChI Key

ZZVUWRFHKOJYTH-UHFFFAOYSA-N

InChI

InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3

IUPAC Name

[2-(diphenylmethoxy)ethyl]dimethylamine

SMILES

CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

Diphenhydramine is a first-generation histamine H1 receptor antagonist (H1 antihistamine) that is widely available as a non-prescription, over-the-counter (OTC) medication. As an OTC medication, diphenhydramine is typically formulated as tablets and creams indicated for use in treating sneezing, runny nose, itchy/watery eyes, itching of nose or throat, insomnia, pruritis, urticaria, insect bites/stings, allergic rashes, and nausea ^9,10,11,15,5.

Additionally, when the use of oral diphenhydramine is impractical, there are also prescription-only formulations such as diphenhydramine injection products that are effective in adults and pediatric patients (other than premature infants and neonates) for: i) the amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after acute allergic reaction symptoms have been controlled, and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated ¹⁴; ii) the active treatment of motion sickness ¹⁴; and iii) use in parkinsonism when oral therapy is impossible or contraindicated, as follows: parkinsonism in the elderly who are unable to tolerate more potent agents; mild cases of parkinsonism in other age groups, and in other cases of parkinsonism in combination with centrally acting anticholinergic agents ¹⁴.

Associated Conditions

Pharmacodynamics

Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties ¹². The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone ¹². Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere ¹². Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone ¹². Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain ¹².

Mechanism of action

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors ^9,10,11,15,5. Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons ^9,10,11,15,5. When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response ^9,10,11,15,5.

Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms ^9,10,11,15,5. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center ^9,10,11,15,5.

Furthermore, H1 receptors are similar to muscarinic receptors ^9,10,11,15,5. Consequently, diphenhydramine also acts as an antimuscarinic ^9,10,11,15,5. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication ^9,10,11,15,5.

Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties ⁹.

Target	Actions	Organism
AHistamine H1 receptor	antagonist	Humans
UMuscarinic acetylcholine receptor M2	antagonist	Humans

Unlock Additional Data

Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more

Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more

Additional Data Available

Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more

Absorption

Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in approximately one hour ^6,13. The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration ^6,13.

Volume of distribution

Diphenhydramine is widely distributed throughout the body, including the CNS ¹⁶. Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range of 3.3 - 6.8 l/kg ¹⁶.

Protein binding

Some prescribing information records the protein binding of diphenhydramine as approximately 78% ¹⁶ while others have suggested the medication is about 80 to 85% ¹³ bound to plasma proteins.

Metabolism

Diphenhydramine undergoes rapid and extensive first-pass metabolism ^16,13,8. In particular, two successive N-demethylations occur wherein diphenhydramine is demethylated to N-desmethyldiphenhydramine (the N-desmethyl metabolite) and then this metabolite is itself demethylated to N,N-didesmethyldiphenhydramine (the N,N-didesmethyl metabolite) ^16,8. Subsequently, acetyl metabolites like N-acetyl-N-desmethyldiphenhydramine are generated via the amine moiety of the N,N-didesmethyl metabolite ⁸. Additionally, the N,N-didesmethyl metabolite also undergoes some oxidation to generate the diphenylmethoxyacetic acid metabolite as well ^16,13,8. The remaining percentage of a dose of administered diphenhydramine is excreted unchanged ^16,13,8. The metabolites are further conjugated with glycine and glutamine and excreted in urine ¹³.

Moreover, studies have determined that a variety of cytochrome P450 isoenzymes are involved in the N-demethylation that characterizes the primary metabolic pathway of diphenhydramine, including CYP2D6, CYP1A2, CYP2C9, and CYP2C19 ⁷. In particular, CYP2D6 demonstrates higher affinity catalysis with the diphenhydramine substrate than the other isoenzymes identified ⁷. Consequently, inducers or inhibitors of these such CYP enzymes may potentially affect the serum concentration and incidence and/or severity of adverse effects associated with exposure to diphenhydramine ⁷.

Route of elimination

The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine ^12,13. Only about 1% of a single dose is excreted unchanged in urine ^12,13. The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites ^12,13.

Half life

The elimination half-life ranges from 2.4-9.3 hours in healthy adults ^16,13. The terminal elimination half-life is prolonged in liver cirrhosis ¹³.

Clearance

Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in the range of 600-1300 ml/min ¹⁶.

Toxicity

Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others ^{10,11,12,13,16}. Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes ¹³. Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse ¹³. Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow ¹⁶.

Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk ¹⁶. This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant ¹⁶.

Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults ¹⁶. Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects ¹³. Avoid use in elderly patients with confusion ¹³.

The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) ¹⁶.

After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease ¹⁶. However, the mean plasma clearance and apparent volume of distribution were not significantly affected ¹⁶.

LD₅₀=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Diphenhydramine H1-Antihistamine Action	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Unlock Additional Data
(R)-warfarin	The metabolism of (R)-warfarin can be decreased when combined with Diphenhydramine.
(S)-Warfarin	The metabolism of (S)-Warfarin can be decreased when combined with Diphenhydramine.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine	The metabolism of Diphenhydramine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1,10-Phenanthroline	The therapeutic efficacy of Diphenhydramine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine	2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Diphenhydramine.
2,5-Dimethoxy-4-ethylthioamphetamine	2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Diphenhydramine.
4-Bromo-2,5-dimethoxyamphetamine	4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Diphenhydramine.
4-Methoxyamphetamine	The risk or severity of adverse effects can be increased when Diphenhydramine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of adverse effects can be increased when Diphenhydramine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole	The risk or severity of adverse effects can be increased when Diphenhydramine is combined with 7-Nitroindazole.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

Learn more

Severity

A severity rating for each drug interaction, from minor to major.

Learn more

Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

Learn more

Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

Learn more

Food Interactions

Avoid alcohol.
Take with food.

References

Synthesis Reference

Alison B. Lukacsko, Joseph J. Piala, "Effect of a combination of a terbutaline, diphenhydramine and ranitidine composition on gastrointestinal injury produced by nonsteroidal anti-inflammatory compositions." U.S. Patent US5260333, issued December, 1983.

US5260333

General References

Raphael GD, Angello JT, Wu MM, Druce HM: Efficacy of diphenhydramine vs desloratadine and placebo in patients with moderate-to-severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2006 Apr;96(4):606-14. [PubMed:16680933]
Abdi A, Rose E, Levine M: Diphenhydramine overdose with intraventricular conduction delay treated with hypertonic sodium bicarbonate and i.v. lipid emulsion. West J Emerg Med. 2014 Nov;15(7):855-8. doi: 10.5811/westjem.2014.8.23407. Epub 2014 Sep 19. [PubMed:25493135]
Halpert AG, Olmstead MC, Beninger RJ: Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002 Jan;26(1):61-7. [PubMed:11835984]
Jaju BP, Wang SC: Effects of diphenhydramine and dimenhydrinate on vestibular neuronal activity of cat: a search for the locus of their antimotion sickness action. J Pharmacol Exp Ther. 1971 Mar;176(3):718-24. [PubMed:4329456]
Flake ZA, Scalley RD, Bailey AG: Practical selection of antiemetics. Am Fam Physician. 2004 Mar 1;69(5):1169-74. [PubMed:15023018]
Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97. [PubMed:2866055]
Akutsu T, Kobayashi K, Sakurada K, Ikegaya H, Furihata T, Chiba K: Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos. 2007 Jan;35(1):72-8. doi: 10.1124/dmd.106.012088. Epub 2006 Oct 4. [PubMed:17020955]
Rodrigues WC, Castro C, Catbagan P, Moore C, Wang G: Immunoassay screening of diphenhydramine (Benadryl(R)) in urine and blood using a newly developed assay. J Anal Toxicol. 2012 Mar;36(2):123-9. doi: 10.1093/jat/bkr015. [PubMed:22337782]
StatPearls [Internet]: Diphenhydramine [Link]
Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Tablets Patient Information [Link]
Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Cream Monograph [Link]
Electronic Medicines Compendium: Boots Sleepeaze (diphenhydramine hydrochloride) 50mg Tablets Monograph [Link]
Electronic Medicines Compendium: Nytol One-A-Night (diphenhydramine hydrochloride) Monograph [Link]
Diphenhydramine Hydrochloride Injection, USP FDA Label [File]
DIPHENHYDRAMINE- diphenhydramine hcl tablet, coated DailyMed FDA Label [File]
Benylin Chesty Coughs UK MHRA Product Information [File]

External Links

Human Metabolome Database: HMDB0001927
KEGG Drug: D00300
KEGG Compound: C06960
PubChem Compound: 3100
PubChem Substance: 46505484
ChemSpider: 2989
BindingDB: 50017674
ChEBI: 4636
ChEMBL: CHEMBL657
Therapeutic Targets Database: DAP000490
PharmGKB: PA449349
Guide to Pharmacology: GtP Drug Page
HET: 2PM
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Diphenhydramine

ATC Codes

D04AA32 — Diphenhydramine

R06AA02 — Diphenhydramine

D04AA33 — Diphenhydramine methylbromide

R06AA52 — Diphenhydramine, combinations

AHFS Codes

04:04.04 — Ethanolamine Derivatives
04:04.00 — First Generation Antihistamines

PDB Entries

2aot

MSDS

Download (73.5 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Not Yet Recruiting	Treatment	Atopic Dermatitis (AD)	1
1	Active Not Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL) / Chronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL)	1
1	Active Not Recruiting	Treatment	Diseases of Oesophagus Stomach and Duodenum	1
1	Active Not Recruiting	Treatment	Multiple Myeloma (MM)	1
1	Completed	Not Available	Autonomic Failure / Orthostatic Hypotension	1
1	Completed	Not Available	Healthy Volunteers	1
1	Completed	Not Available	Therapeutic Equivalence	1
1	Completed	Basic Science	Allergic Rhinitis (AR)	1
1	Completed	Basic Science	Healthy Volunteers	1
1	Completed	Basic Science	Nasal Congestion	1
1	Completed	Other	Healthy Volunteers	1
1	Completed	Screening	Fibrosis	1
1	Completed	Treatment	Healthy Volunteers	4
1	Completed	Treatment	Major Depressive Disorder (MDD)	1
1	Completed	Treatment	Pain	1
1	Completed	Treatment	Pain / Pharmacology, Clinical	1
1	Completed	Treatment	Restless Legs Syndrome (RLS)	1
1	Completed	Treatment	Tumors, Solid	1
1	Recruiting	Other	Healthy Volunteers / Sleep	1
1	Recruiting	Treatment	Graft Versus Host Disease (GVHD) / Sickle Cell Disorders	1
1	Recruiting	Treatment	Neoplasms Malignant	1
1	Recruiting	Treatment	Pompe's Disease	1
1	Terminated	Not Available	Healthy Male Volunteers	1
1	Terminated	Basic Science	Drug Metabolism, Poor, CYP2D6-RELATED	1
1	Terminated	Treatment	Alpha-1 Antitrypsin Deficiency	1
1	Terminated	Treatment	Transplantation, Liver	1
1, 2	Active Not Recruiting	Treatment	Liver Transplanted Patients / Living Donor (of the Respective Liver Transplant Recipient)	1
1, 2	Active Not Recruiting	Treatment	Lung Cancers	1
1, 2	Completed	Treatment	Kidney Diseases / Transplantation, Kidney	1
1, 2	Completed	Treatment	Leukemia, Acute Lymphocytic (ALL) / Leukemia, Acute Myelogenous (AML) / Leukemia, Chronic Myelogenous (CML) / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)	1
1, 2	Completed	Treatment	Post-Traumatic Headaches	1
1, 2	Recruiting	Treatment	Adult Living Donor Kidney Transplant Recipients / Living Kidney Donors / Transplant, Kidney	1
1, 2	Terminated	Treatment	Colo-rectal Cancer / Colon/Rectal Cancer / Colon/Rectal Cancer Rectal Cancer / Rectal Carcinoma	1
2	Active Not Recruiting	Treatment	Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma / Non-Hodgkin's Lymphoma (NHL)	1
2	Active Not Recruiting	Treatment	Systemic Sclerosis-Associated PAH / Systemic Sclerosis-Associated Pulmonary Arterial Hypertension	1
2	Completed	Not Available	Malignancies / Tumors, Solid	1
2	Completed	Supportive Care	Stomatitis, Aphthous	1
2	Completed	Treatment	Atopic Dermatitis (AD) / Pruritus	1
2	Completed	Treatment	Blood Cancers / Chronic Lymphocytic Leukaemia (CLL) / Graft Versus Host Disease (GVHD) / Hodgkins Disease (HD) / Leukemias / Malignancies / Non-Hodgkin's Lymphoma (NHL) / Smith-Magenis Syndrome	1
2	Completed	Treatment	Blood and Marrow Transplant (BMT) / Multiple Myeloma (MM) / Transplantation, Autologous / Transplantation, Homologous	1
2	Completed	Treatment	Breast Cancer	1
2	Completed	Treatment	Cerebrovascular Accident, Acute / Edema of the cerebrum	1
2	Completed	Treatment	Chronic Idiopathic Urticaria	1
2	Completed	Treatment	Depression	1
2	Completed	Treatment	Endometrial Cancer	1
2	Completed	Treatment	Leukemia, Mast-Cell / Mantle Cell Lymphoma (MCL)	1
2	Completed	Treatment	Malignant Lymphomas	1
2	Completed	Treatment	Multiple Myeloma (MM)	1
2	Completed	Treatment	Nephritis, Lupus	1
2	Completed	Treatment	Rejection, Transplant	1
2	Completed	Treatment	Renal Cancers	1
2	Completed	Treatment	Renal Cell Adenocarcinoma	1
2	Completed	Treatment	Restless Legs Syndrome (RLS)	1
2	Completed	Treatment	Systemic Lupus Erythematosus (SLE)	1
2	Completed	Treatment	Vulvodynia	1
2	Not Yet Recruiting	Treatment	Emergency Department / Headache Disorders, Primary / Pain Management	1
2	Not Yet Recruiting	Treatment	Oncology Patients Receiving Chemotherapy	1
2	Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL)	1
2	Recruiting	Treatment	Alcohol Dependence	1
2	Recruiting	Treatment	Cocaine-Related Disorders	1
2	Recruiting	Treatment	HNSCC / HPV-Related Squamous Cell Carcinoma	1
2	Recruiting	Treatment	Transplant, Kidney	1
2	Terminated	Supportive Care	Nausea / Unspecified Childhood Solid Tumor, Protocol Specific / Vomiting	1
2	Terminated	Treatment	Blood and Marrow Transplant (BMT) / Diffuse Large B-Cell / Lymphoma, B-Cell / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphoma, Non-Hodgkin / Non-Hodgkin's Lymphoma (NHL)	1
2	Terminated	Treatment	Hepatitis B Chronic Infection	1
2	Terminated	Treatment	Mucositis / Neoplasms	1
2	Terminated	Treatment	Prostate Cancer	1
2	Terminated	Treatment	T-cell Type Acute Leukemia-Precursor T-lymphoblastic Lymphoma/Leukaemia	1
2	Terminated	Treatment	Transplantation, Kidney	1
2	Withdrawn	Treatment	Painful Diabetic Neuropathy (PDN)	1
2, 3	Completed	Treatment	Stomatitis	1
2, 3	Completed	Treatment	Systemic Lupus Erythematosus (SLE)	1
2, 3	Terminated	Treatment	Systemic Lupus Erythematosus (SLE)	1
3	Active Not Recruiting	Supportive Care	Malignant Head and Neck Neoplasm / Mucositis / Radiation-Induced Disorder	1
3	Active Not Recruiting	Treatment	Plasma Cell Myeloma	1
3	Completed	Treatment	Acute Oral Mucositis Pain	1
3	Completed	Treatment	Acute Urticaria	2
3	Completed	Treatment	Chronic Idiopathic Urticaria	1
3	Completed	Treatment	Elective Caesarean Section Surgeries	1
3	Completed	Treatment	Healthy Volunteers	1
3	Completed	Treatment	Migraine	1
3	Completed	Treatment	Nephritis, Lupus	1
3	Recruiting	Treatment	Post-Traumatic Headaches	1
3	Terminated	Treatment	Anxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders	1
3	Unknown Status	Treatment	Insomnia	1
3	Withdrawn	Treatment	Coughing / Inflammatory Reaction / Rhinitis	1
4	Active Not Recruiting	Supportive Care	Adjunct Anesthesia Medication / Colonoscopy	1
4	Completed	Diagnostic	Asthma	1
4	Completed	Prevention	Hypnotic / Specified Sedative	1
4	Completed	Treatment	Bacterial Infections	1
4	Completed	Treatment	Headache	1
4	Completed	Treatment	Migraine	2
4	Completed	Treatment	Migraine / Nausea / Restlessness	1
4	Completed	Treatment	Nasal Congestion	1
4	Completed	Treatment	Extra-pyramidal symptoms / Nausea	1
4	Completed	Treatment	Neurogenic Intermittent Claudication / Spinal Stenosis of Lumbar Region	1
4	Completed	Treatment	Occasional Sleeplessness	1
4	Completed	Treatment	Prostate Cancer	1
4	Completed	Treatment	Sedation	1
4	Completed	Treatment	Sleep	1
4	Enrolling by Invitation	Treatment	Primary Total Hip Arthroplasty / Primary Total Knee Arthroplasty	1
4	Recruiting	Treatment	Headache	1
4	Terminated	Treatment	Migraine	1
Not Available	Active Not Recruiting	Other	Pain	1
Not Available	Active Not Recruiting	Screening	Alcohol Dependence	1
Not Available	Completed	Basic Science	Hyperalgesia	1
Not Available	Completed	Other	Pain, Neuropathic	1
Not Available	Completed	Prevention	General Surgery / Pain	1
Not Available	Completed	Prevention	Headache	1
Not Available	Completed	Supportive Care	Focus of Study: Absorption of the Three Components in the Topical ABH Gel in Healthy Volunteers, and Determine if There Are Any Adverse Effects / Healthy Volunteers	1
Not Available	Completed	Supportive Care	Nausea / Vomiting	1
Not Available	Completed	Treatment	Benign Paroxysmal Positional Vertigo (BPPV)	1
Not Available	Completed	Treatment	Endometriosis	1
Not Available	Completed	Treatment	Endoscopy / Sedation	1
Not Available	Completed	Treatment	Hip Fracture Surgery / Post Operative Pain Control	1
Not Available	Completed	Treatment	Itching	1
Not Available	Completed	Treatment	Pain	1
Not Available	Recruiting	Treatment	Alcohol-Related Disorders / Brain Injury / Depression / Disease, Chronic / Mild Cognitive Impairment (MCI) / Pain / Posttraumatic Stress Disorders / Quality of Life / Substance-Related Disorders / Suicidal Thoughts / Wounds and Injuries	1
Not Available	Recruiting	Treatment	Migraine	1
Not Available	Suspended	Diagnostic	Bulimia Nervosa / Catechol-O-methyltransferase / Dopamine / Eating Disorders / Reward	1
Not Available	Terminated	Not Available	Pain, Chronic	1
Not Available	Terminated	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
Not Available	Terminated	Treatment	Primary Headaches (Includes Migraines, Tension, Cluster Headaches)	1
Not Available	Unknown Status	Supportive Care	Endoscopic Retrograde Cholangiopancreatography (ERCP) / Endoscopic Ultrasound (EUS)	1
Not Available	Withdrawn	Treatment	Post Operative Nausea and Vomiting (PONV) / Rescue Emetic Therapy	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Advance Pharmaceutical
Advent Pharmaceuticals Inc.
Amend
APP Pharmaceuticals
A-S Medication Solutions LLC
Auriga Pharmaceuticals LLC
Barr Pharmaceuticals
Baxter International Inc.
Bergen Brunswig
Bioniche Pharma
Bryant Ranch Prepack
C.O. Truxton Inc.
Cardinal Health
Carlisle Laboratories Inc.
Chattem Chemicals Inc.
Concord Labs
Consolidated Midland Corp.
Contract Pharm
CVS Pharmacy
Darby Dental Supply Co. Inc.
Dept Health Central Pharmacy
Direct Dispensing Inc.
DispenseXpress Inc.
Dispensing Solutions
Diversified Healthcare Services Inc.
Eon Labs
Equaline Vitamins
Fusion Pharmaceuticals LLC
General Injectables and Vaccines Inc.
GlaxoSmithKline Inc.
Goldline Laboratories Inc.
Group Health Cooperative
Hawthorn Pharmaceuticals
Heartland Repack Services LLC
Hospira Inc.
Innoviant Pharmacy Inc.
Ivax Pharmaceuticals
Kraft Pharmaceutical Co. Inc.
Liberty Pharmaceuticals
Lnk International Inc.
Major Pharmaceuticals
Martin Surgical Supply
McNeil Laboratories
Medique Products
Medtech Labs
Merit Pharmaceuticals
Midlothian Labs
Mississippi State Dept Health
Murfreesboro Pharmaceutical Nursing Supply
Nexgen Pharma Inc.
North Safety Products
Nucare Pharmaceuticals Inc.
Patient First Corp.
PCA LLC
PD-Rx Pharmaceuticals Inc.
Perrigo Co.
Pfizer Inc.
Pharmaceutical Association
Pharmedix
Physicians Total Care Inc.
Poly Pharmaceuticals Inc.
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Prescript Pharmaceuticals
Procter & Gamble
Provident Pharmaceuticals LLC
Remedy Repack
Rite Aid Corp.
River's Edge Pharmaceuticals
Rugby Laboratories
Sandhills Packaging Inc.
Scientific Laboratories Inc.
Silarx Pharmaceuticals
Southwood Pharmaceuticals
St Mary's Medical Park Pharmacy
Tya Pharmaceuticals
UDL Laboratories
United Research Laboratories Inc.
Vangard Labs Inc.
Walgreen Co.

Dosage forms

Form	Route	Strength
Kit	Topical
Capsule; kit	Oral
Cream	Topical	20 mg/1mL
Cream	Topical	2.0 mL/100mL
Liquid	Oral	12.5 mg
Liquid	Oral	12.5 mg/5mL
Capsule, gelatin coated	Oral
Powder	Oral	25 mg/1
Solution	Oral
Gel	Topical	2 g/100g
Cream	Topical	2 %
Patch	Topical
Injection, solution	Intramuscular; Intravenous	50 mg/1mL
Solution	Oral	12.5 mg
Tablet, coated	Oral	25 mg/1
Strip	Oral	25 mg/1
Tablet, chewable	Oral
Liquid	Oral
Cream	Topical
Elixir	Oral
Solution	Topical
Gel	Topical	20 mg/1mL
Gel	Topical
Tablet	Oral	25 mg/250mg
Lotion	Topical
Suspension	Topical
Syrup	Oral
Tablet	Oral	12.5 mg/1
Tablet, chewable	Oral	12.5 mg/1
Suspension	Oral
Kit; tablet	Oral
Ointment	Topical
Spray	Topical
Liquid	Topical
Kit	Oral	0.75 g/0.75g
Kit	Oral	0.86 g/0.86g
Capsule, coated	Oral	25 mg/1
Injection, solution	Intravenous	50 mg/1mL
Tablet	Oral	25 mg
Tablet, coated	Oral	25 mg/ 11
Capsule, liquid filled	Oral	20 mg/1
Tablet	Oral	50 mg/1
Capsule, gelatin coated	Oral	25 mg/1
Liquid	Intravenous
Capsule		25 mg/1
Capsule		50 mg/1
Capsule	Oral	25 mg/1
Capsule	Oral	50 mg/1
Capsule, liquid filled	Oral	50 mg/1
Elixir	Oral	25 mg/10mL
Injection	Intramuscular	50 mg/1mL
Injection	Intramuscular; Intravenous	50 mg/1mL
Injection	Parenteral	50 mg/1mL
Liquid	Oral	25 mg/10mL
Liquid	Oral	6.25 mg/1mL
Solution	Oral	25 mg/10mL
Solution	Oral	50 mg/20mL
Tablet, film coated	Oral	25 mg/1
Liquid	Intramuscular; Intravenous
Tablet, chewable	Oral
Syrup	Oral
Gel	Topical	2 mg/100mL
Capsule, liquid filled	Oral
Capsule, liquid filled	Oral	25 mg/1
Solution	Oral	50 mg/40mL
Kit	Oral
Aerosol, spray	Topical
Powder	Oral
Liquid	Topical	20.3 g/1L
Spray	Topical	2 g/100mL
Gel	Topical	2.03 g/100g
Aerosol	Topical
Strip	Oral
Tablet, orally disintegrating	Oral	12.5 mg/1
Liniment	Topical
Liquid	Oral	50 mg/20mL
Capsule, gelatin coated	Oral	50 mg/1
Lozenge	Oral
Strip	Oral
Capsule	Oral	25 mg
Liquid	Oral	50 mg/30mL
Solution	Oral	50 mg
Tablet, film coated	Oral	50 mg/1
Liquid	Oral	50 mg
Capsule, liquid filled	Oral	50 mg/21
Solution	Oral
Tablet	Oral
Granule, for solution	Oral
Tablet, coated	Oral
Capsule	Oral
Cream	Topical
Solution	Oral	12.5 mg/5mL
Syrup	Oral	12.5 mg/5mL
Tablet	Oral
Gel	Topical	20.5 mg/1mL
Liquid	Oral
Plaster	Topical
Solution	Intramuscular; Intravenous
Gel	Topical	2 g/100mL
Gel	Topical	.2 g/10mL
Solution	Oral	50 mg/30mL
Tablet	Oral	50 mg
Tablet, coated	Oral	50 mg/1
Gel	Topical
Tablet, multilayer	Oral
Tablet, multilayer, extended release	Oral
Gel	Topical	20 mg/1g
Spray	Topical	20 mg/1mL
Capsule, coated	Oral
Tablet	Oral	25 mg/1
Tablet, film coated	Oral
Tablet, delayed release	Oral
Capsule	Oral
Tablet, chewable	Oral	25 mg/1
Powder, for solution	Oral
Capsule, gelatin coated	Oral	50 mg/21
Spray	Topical

Prices

Unit description	Cost	Unit
DiphenhydrAMINE HCl 100 50 mg capsule Bottle	13.99USD	bottle
Diphenhydramine 50 mg/ml	3.94USD	ml
Diphenhydramine 50 mg/ml vial	1.69USD	ml
DiphenhydrAMINE HCl 50 mg/ml vial	1.44USD	vial
Dytan 25 mg tablet chewable	1.37USD	tablet
Benadryl 50 mg/ml vial	1.36USD	ml
Diphenmax 25 mg tablet	1.24USD	tablet
Benadryl allergy 25 mg strips	0.45USD	strip
Unisom sleep aid tablet	0.34USD	tablet
Sleep-eze 3 tablet	0.29USD	tablet
Compoz 50 mg tablet	0.27USD	tablet
Sominex max str 50 mg caplet	0.27USD	caplet
Benadryl allergy fastmelt tablet	0.26USD	tablet
Unisom 25 mg sleeptabs	0.25USD	tablet
Unisom 50 mg sleepgels	0.25USD	each
Unisom sleepmelts 25 mg tablet	0.24USD	tablet
Nytol 25 mg tablet	0.23USD	tablet
Benadryl allergy-sinus caplet	0.22USD	caplet
Compoz 25 mg gelcap	0.2USD	capsule
Benadryl allergy 25 mg softgel	0.19USD	softgel capsule
Benadryl allergy 25 mg ultratab	0.19USD	tablet
Benadryl allergy-cold kapgels	0.19USD	each
Benadryl allergy-sinus kapgels	0.19USD	each
Benadryl-d allergy-sinus ultratab	0.19USD	tablet
Diphenhydramine hcl powder	0.17USD	g
Eql allergy 25 mg tablet	0.17USD	tablet
Nighttime sleep aid 25 mg cplt	0.17USD	caplet
Banophen anti-itch 2% cream	0.16USD	g
Benadryl itch relief stick	0.16USD	ml
Sominex 25 mg tablet	0.16USD	tablet
Benadryl allergy 25 mg kapgels	0.15USD	each
Allergy 25 mg tablet	0.14USD	tablet
Benadryl 25 mg kapseals	0.14USD	each
Benadryl itch stopping crm	0.14USD	g
DiphenhydrAMINE HCl 25 mg capsule	0.13USD	capsule
Diphenhist with zinc cream	0.12USD	g
Ra allergy 25 mg tablet	0.12USD	tablet
CVS Pharmacy allergy 25 mg tablet	0.11USD	tablet
Diphenhydramine 25 mg minitab	0.11USD	tablet
Simply sleep 25 mg caplet	0.11USD	caplet
Sleep ii tablet	0.11USD	tablet
Diphenhydramine 50 mg capsule	0.1USD	capsule
Benadryl 2% spray	0.09USD	ml
Diphenhist 50 mg tablet	0.09USD	tablet
Genahist 25 mg tablet	0.09USD	tablet
Ra sleep tablet	0.09USD	tablet
Banophen 25 mg tablet	0.08USD	tablet
Wal-dryl anti-itch spray	0.08USD	ml
CVS Pharmacy allergy 25 mg caplet	0.07USD	caplet
Nighttime sleep aid 25 mg caplet	0.07USD	caplet
CVS Pharmacy itch relief spray	0.06USD	ml
Diphen 25 mg capsule	0.06USD	capsule
Diphenhist 25 mg caplet	0.06USD	caplet
Benadryl anti-itch 0.45% gel	0.05USD	g
Diphenhydramine 50 mg caplet	0.05USD	caplet
Benadryl itch stopping gel	0.04USD	g
Child benadryl-d aller-sin liquid	0.04USD	ml
Diphenhydramine 25 mg capsule	0.04USD	capsule
Vicks 44d cough & head liquid	0.03USD	ml
Vicks 44e cough & chest liquid	0.03USD	ml
Banophen allergy liquid	0.02USD	ml
Diphenhydramine 25 mg tablet	0.02USD	tablet
Ra anti-tussive dm syrup	0.02USD	ml
Siladryl 12.5 mg/5 ml liquid	0.02USD	ml
Silphen cough syrup	0.02USD	ml
Silphen dm cough syrup	0.02USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
Unlock Additional Data
US8883849	No	2014-11-11	2022-01-17
US9155718	No	2015-10-13	2022-01-17
US8263647	No	2012-09-11	2022-05-30

Additional Data Available

Filed On

The date on which a patent was filed with the relevant government.

Learn more

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	161-162	Martin, H., Hafliger, F.,Gatzi, K.and Grob, A.; U.S. Patent 2,397,799; April 2,1946; assigned to J.R. Geigy AG, Switzerland. Rieveschl, G. Jr.; U.S. Patent 2,421,714; June 3,1947; assigned to Parke, Davis & Co. Rieveschl, G. Jr.; U.S. Patent 2,427,878; September 23,1947; assigned to Parke, Davis & Company.
boiling point (°C)	150-165 °C at 2.00E+00 mm Hg	PhysProp
water solubility	3060 mg/L (at 37 °C)	BEILSTEIN
logP	3.27	HANSCH,C ET AL. (1995)
pKa	8.98	SANGSTER (1994)

Predicted Properties

Property	Value	Source
Water Solubility	0.0752 mg/mL	ALOGPS
logP	3.44	ALOGPS
logP	3.65	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Basic)	8.87	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	12.47 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	79.93 m³·mol^-1	ChemAxon
Polarizability	29.86 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9898
Blood Brain Barrier	+	0.9381
Caco-2 permeable	+	0.8744
P-glycoprotein substrate	Substrate	0.6211
P-glycoprotein inhibitor I	Non-inhibitor	0.6632
P-glycoprotein inhibitor II	Non-inhibitor	0.8381
Renal organic cation transporter	Inhibitor	0.7752
CYP450 2C9 substrate	Non-substrate	0.7897
CYP450 2D6 substrate	Substrate	0.8919
CYP450 3A4 substrate	Substrate	0.6173
CYP450 1A2 substrate	Inhibitor	0.8306
CYP450 2C9 inhibitor	Non-inhibitor	0.9144
CYP450 2D6 inhibitor	Inhibitor	0.8932
CYP450 2C19 inhibitor	Non-inhibitor	0.9039
CYP450 3A4 inhibitor	Non-inhibitor	0.934
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.7293
Ames test	Non AMES toxic	0.9132
Carcinogenicity	Non-carcinogens	0.6495
Biodegradation	Not ready biodegradable	0.9253
Rat acute toxicity	2.7846 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.536
hERG inhibition (predictor II)	Inhibitor	0.6318

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
GC-MS Spectrum - EI-B	GC-MS	splash10-0a4i-9100000000-7b9eb1f702c76f6b6062
Mass Spectrum (Electron Ionization)	MS	splash10-0a4i-9200000000-b9014c8fc8ccbba24163
MS/MS Spectrum - Quattro_QQQ 10V, N/A	LC-MS/MS	splash10-0006-0090000000-a71e531b49571f09ab25
MS/MS Spectrum - Quattro_QQQ 25V, N/A	LC-MS/MS	splash10-00kk-0980000000-cce91896f34562beeffa
MS/MS Spectrum - Quattro_QQQ 40V, N/A	LC-MS/MS	splash10-001i-1900000000-4c29bd5e0eab94596eaa
MS/MS Spectrum - EI-B (Unknown) , Positive	LC-MS/MS	splash10-0a4i-9100000000-ab642e8f86de11af896c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-000t-0910000000-3576ca5ec77ab87354ec
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-0ccd6de9ca58593fd490
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-3568aae4c27ffe333c0e
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-22e0c745355c836f1535
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-6bb69a66a343440c64f8
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-1b87d83415d22bb17f1b
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0gb9-0900000000-50251362d768cd1b1c4f
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0gb9-0900000000-9f37a733a05f5b01d313
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-7d73b95ed09ea2d72260
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0gb9-2900000000-1666a8ab5a6d81c0bd01
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-014i-0900000000-3f31841d858381760f03
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-014i-0900000000-de872e048c7e12cef490
LC-MS/MS Spectrum - LC-ESI-ITFT , positive	LC-MS/MS	splash10-014i-0900000000-de872e048c7e12cef490
MS/MS Spectrum - , positive	LC-MS/MS	splash10-014i-0900000000-789a4a3fe118d5bf2456
MS/MS Spectrum - , positive	LC-MS/MS	splash10-014i-2900000000-8ef94659f614b9ff24ca
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0002-2950000000-7c7a9841f2f0b6428d69
1H NMR Spectrum	1D NMR	Not Applicable
[1H,13C] 2D NMR Spectrum	2D NMR	Not Applicable

Taxonomy

Description: This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom: Organic compounds
Super Class: Benzenoids
Class: Benzene and substituted derivatives
Sub Class: Diphenylmethanes
Direct Parent: Diphenylmethanes
Alternative Parents: Benzylethers / Trialkylamines / Dialkyl ethers / Organopnictogen compounds / Hydrocarbon derivatives
Substituents: Diphenylmethane / Benzylether / Tertiary aliphatic amine / Tertiary amine / Ether / Dialkyl ether / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework: Aromatic homomonocyclic compounds
External Descriptors: tertiary amino compound, ether (CHEBI:4636) / a small molecule (CPD-10890)

Targets

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	11.7	N/A	N/A	12065734
Ki (nM)	13.5	N/A	N/A	12065734
Ki (nM)	14.08	N/A	N/A	2904784
Ki (nM)	14.79	N/A	N/A	21944853
Ki (nM)	62	N/A	N/A	6146381

Details1. Histamine H1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Histamine receptor activity
Specific Function: In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name: HRH1
Uniprot ID: P35367
Uniprot Name: Histamine H1 receptor
Molecular Weight: 55783.61 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Piao H, Nagai S, Tsurumaki T, Niki T, Higuchi H: Potentiation by neuropeptide Y of histamine H1 receptor-mediated contraction in rat blood vessels. Vascul Pharmacol. 2007 Apr;46(4):260-70. Epub 2006 Oct 27. [PubMed:17169617]
Kesiova M, Alexandrova A, Yordanova N, Kirkova M, Todorov S: Effects of diphenhydramine and famotidine on lipid peroxidation and activities of antioxidant enzymes in different rat tissues. Pharmacol Rep. 2006 Mar-Apr;58(2):221-8. [PubMed:16702624]
Hasala H, Moilanen E, Janka-Junttila M, Giembycz MA, Kankaanranta H: First-generation antihistamines diphenhydramine and chlorpheniramine reverse cytokine-afforded eosinophil survival by enhancing apoptosis. Allergy Asthma Proc. 2007 Jan-Feb;28(1):79-86. [PubMed:17390763]
Wang Z, Woolverton WL: Self-administration of cocaine-antihistamine combinations: super-additive reinforcing effects. Eur J Pharmacol. 2007 Feb 28;557(2-3):159-60. Epub 2006 Dec 1. [PubMed:17196194]
Ishikawa T, Takechi K, Rahman A, Ago J, Matsumoto N, Murakami A, Kamei C: Influences of histamine H1 receptor antagonists on maximal electroshock seizure in infant rats. Biol Pharm Bull. 2007 Mar;30(3):477-80. [PubMed:17329841]
Havas TE, Cole P, Parker L, Oprysk D, Ayiomamitis A: The effects of combined H1 and H2 histamine antagonists on alterations in nasal airflow resistance induced by topical histamine provocation. J Allergy Clin Immunol. 1986 Nov;78(5 Pt 1):856-60. [PubMed:2878016]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	120	N/A	N/A	1346637

Details2. Muscarinic acetylcholine receptor M2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: G-protein coupled acetylcholine receptor activity
Specific Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name: CHRM2
Uniprot ID: P08172
Uniprot Name: Muscarinic acetylcholine receptor M2
Molecular Weight: 51714.605 Da

References

Liu H, Zheng Q, Farley JM: Antimuscarinic actions of antihistamines on the heart. J Biomed Sci. 2006 May;13(3):395-401. [PubMed:16453179]

Enzymes

Details1. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J: In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos. 1998 Jun;26(6):536-9. [PubMed:9616188]
Akutsu T, Kobayashi K, Sakurada K, Ikegaya H, Furihata T, Chiba K: Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos. 2007 Jan;35(1):72-8. doi: 10.1124/dmd.106.012088. Epub 2006 Oct 4. [PubMed:17020955]
Lessard E, Yessine MA, Hamelin BA, Gauvin C, Labbe L, O'Hara G, LeBlanc J, Turgeon J: Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. J Clin Psychopharmacol. 2001 Apr;21(2):175-84. [PubMed:11270914]
Flockhart Table of Drug Interactions [Link]

Details2. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Connecticut's Official State Website: CYP Chart [File]

Details3. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name: CYP2C19
Uniprot ID: P33261
Uniprot Name: Cytochrome P450 2C19
Molecular Weight: 55930.545 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]

Details4. Prostaglandin G/H synthase 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Prostaglandin-endoperoxide synthase activity
Specific Function: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name: PTGS1
Uniprot ID: P23219
Uniprot Name: Prostaglandin G/H synthase 1
Molecular Weight: 68685.82 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]

Transporters

Details1. Solute carrier family 22 member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Quaternary ammonium group transmembrane transporter activity
Specific Function: Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name: SLC22A2
Uniprot ID: O15244
Uniprot Name: Solute carrier family 22 member 2
Molecular Weight: 62579.99 Da

References

Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]

Details2. Solute carrier family 22 member 5

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Symporter activity
Specific Function: Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name: SLC22A5
Uniprot ID: O76082
Uniprot Name: Solute carrier family 22 member 5
Molecular Weight: 62751.08 Da

References

Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [PubMed:11160873]

Drug created on June 13, 2005 07:24 / Updated on December 11, 2019 03:37

Diphenhydramine

Identification

Structure for Diphenhydramine (DB01075)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

Enzymes

References

References

References

References

Transporters

References

References